Gene therapy for chronic pain management

Despite significant advances in identifying molecular targets for chronic pain over the past two decades, many remain difficult to target with traditional methods. Gene therapies such as antisense oligonucleotides (ASOs), RNA interference (RNAi), CRISPR, and virus-based delivery systems have played crucial roles in discovering and validating new pain targets. While there has been a surge in gene therapy-based clinical trials, those focusing on pain as the primary outcome remain uncommon. This review examines various gene therapy strategies, including ASOs, small interfering RNA (siRNAs), optogenetics, chemogenetics, and CRISPR, and their delivery methods targeting primary sensory neurons and non-neuronal cells, including glia and chondrocytes. We also explore emerging gene therapy tools and highlight gene therapy’s clinical potential in pain management, including trials targeting pain-related diseases. Advances in single-cell analysis of sensory neurons and non-neuronal cells, along with the development of new delivery tools, are poised to accelerate the application of gene therapy in pain medicine. [Display omitted] In this review article, Li et al. discuss various gene therapy strategies and their delivery methods targeting primary sensory neurons and non-neuronal cells, including glia and chondrocytes. They also highlight recent advances in gene therapy, including CRISPR-Cas and RNA-based techniques, as well as clinical trials targeting pain-related diseases.